Our present understanding of the neuronal and synaptic organizataion of the vertebrate oculomotor system has derived largely from the study of mammalian eye movements. Past efforts have centered around a detailed morphological and physiological analysis of the individual neuronal elements within the oculomotor system in order to better interpret neuronal form in view of cellular function. This overall goal will be continued with major reliance on the use of intracellular recording and HRP staining of identified neurons in the alert animal paradigm. This approach is to be substantially strengthened by including a carefully planned phylogenetic analysis of particular neurons and circuits in the coulomotor system. Assuming that a conservative neuronal plan extends throughout vertebrate oculomotor phylogeny, it is argued that knowledge of vertical and horizontal eye movement in antecedent vertebrates can contribute to a better understanding of basic principles and concepts underlying descendent CNS organization. The research plan encompasses 5 specific areas each of which employ similar experimental approaches, but utilize quite different species. (1) Phylogeny of the abducens nucleus with specific emphasis on internuclear neuron organization will be studied extensively from its first appearance in vertebrates up to, and including, mammals. (2) Synaptic and ionic mechanisms underlying horizontal and vertical saccadic organization will be examined largely in fish. (3) Inhibitory and excitatory second-order vestibulo-ocular neurons will be explored initially in fish, but also in descendent species with focus on their relationship to the phylogenetic origin, history and role of the trochlear motor nucleus in eye movement. (4) Mammalian oculomotor internuclear neurons will be studied and their origin will be sought in antecedent species. (5) Neuronal and synaptic effects of axotomy and regeneration will be evaluated centrally and in respect to neurogenic and myogenic influences on extraocular muscle fiber differentiation. Overall, the plan is to study homologous neurons and circuitry throughout the evolutionary scale in order to provide a solid basis for clarifying their role in mammals. All work envisioned is consistent with the goal of elucidating important relationships in the oculomotor system underlying gaze control and, concommmitantly, a better understanding of oculomotility disorders.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002007-13
Application #
3256391
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1976-09-30
Project End
1991-09-29
Budget Start
1988-09-30
Budget End
1989-09-29
Support Year
13
Fiscal Year
1988
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Ma, Leung-Hang; Grove, Charlotte L; Baker, Robert (2014) Development of oculomotor circuitry independent of hox3 genes. Nat Commun 5:4221
Straka, Hans; Baker, Robert (2013) Vestibular blueprint in early vertebrates. Front Neural Circuits 7:182
Bianco, Isaac H; Ma, Leung-Hang; Schoppik, David et al. (2012) The tangential nucleus controls a gravito-inertial vestibulo-ocular reflex. Curr Biol 22:1285-95
Lyons, Peter J; Ma, Leung-hang; Baker, Robert et al. (2010) Carboxypeptidase A6 in zebrafish development and implications for VIth cranial nerve pathfinding. PLoS One 5:e12967
Ma, Leung-Hang; Punnamoottil, Beena; Rinkwitz, Silke et al. (2009) Mosaic hoxb4a neuronal pleiotropism in zebrafish caudal hindbrain. PLoS One 4:e5944
Lambert, Francois M; Beck, James C; Baker, Robert et al. (2008) Semicircular canal size determines the developmental onset of angular vestibuloocular reflexes in larval Xenopus. J Neurosci 28:8086-95
Straka, H; Baker, R; Gilland, E (2001) Rhombomeric organization of vestibular pathways in larval frogs. J Comp Neurol 437:42-55
Graf, W; Spencer, R; Baker, H et al. (2001) Vestibuloocular reflex of the adult flatfish. III. A species-specific reciprocal pattern of excitation and inhibition. J Neurophysiol 86:1376-88
Nguyen, L T; Baker, R; Spencer, R F (1999) Abducens internuclear and ascending tract of deiters inputs to medial rectus motoneurons in the cat oculomotor nucleus: synaptic organization. J Comp Neurol 405:141-59
Gilland, E; Miller, A L; Karplus, E et al. (1999) Imaging of multicellular large-scale rhythmic calcium waves during zebrafish gastrulation. Proc Natl Acad Sci U S A 96:157-61

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